The present invention relates to methods for magnesium substitution of crystalline hydroxyapatites that provide heretofore unobtained levels of magnesium incorporation into the hydroxyapatite lattice structure. The present invention also relates to phase-pure magnesium-substituted crystalline hydroxyapatites obtained thereby.
Hydroxyapatite (HAp, chemical formula Ca10(PO4)6(OH)2) has attracted the attention of researchers over the past thirty years as an implant material because of its excellent biocompatibility and bioactivity. HAp has been extensively used in medicine for implant fabrication. It is commonly the material of choice for the fabrication of dense and porous bioceramics. Its general uses include biocompatible phase-reinforcement in composites, coatings on metal implants and granular fill for direct incorporation into human tissue. It has also been extensively investigated for non-medical applications such as a packing material/support for column chromatography, gas sensors and catalysts, as a host material for lasers, and as a plant growth substrate. All properties of HAp, including bioactivity, biocompatibility, solubility and adsorption properties can be tailored within a wide range by controlling qualitatively and quantitatively the ions substituted for Ca2+, PO43− and OH− in the HAp lattice structure.
Magnesium has been known as one of the cationic substitutes for calcium in the HAp lattice structure. Magnesium-substituted HAp can be expressed by the simplified chemical formula:Ca10-xMgx(PO4)6(OH)2
with x/10 representing atom-percent substitution of magnesium ions for calcium ions.
Magnesium is also one of the predominant substitutes for calcium in biological apatites. Enamel, dentin, and bone contain respectively 0.44 wt %, 1.23 wt % and 0.72 wt % magnesium. Accordingly, magnesium-substituted HAp materials (Mg-HAp) are expected to have excellent biocompatibility and properties that can be favorably compared with those of hard tissue. U.S. Pat. No. 6,027,742 and WO 00/03747, for example, disclose the use of Mg-HAp as bone substitutes and for dental applications, respectively.
Increasing concentration of MG in HAp has the following effects on its properties: (a) gradual decrease in crystallinity, (b) increase HPO4 incorporation, and (c) increase in extent of dissolution. Magnesium is closely associated with mineralization of calcified tissues, and indirectly influences mineral metabolism. It has been suggested that magnesium directly stimulates osteoblast proliferation with an effect comparable to that of insulin (a known growth factor for osteoblast). Thus, it becomes possible to tailor the physicochemical properties of HAp, as well as its biocompatibility and bioactivity, by controlling the Mg substitution of the HAp lattice structure.
Because the optimum amounts of magnesium in artificial HAp ceramics can vary with different applications, the capability to control precisely the amounts of magnesium in HAp in the widest possible range by controlling the synthesis procedure is of primary importance. Mg-HAp powders have been prepared by precipitation and hydrolysis methods with the replacement of calcium by magnesium limited to no more than 0.3 wt %.
Bigi et al., J. Inorg. Biochem. 49, 69-78(1993) disclosed the synthesis of crystalline Mg-HAp powders with up to about 30 atom-percent (about 7.5 wt %) of magnesium under hydrothermal conditions at 120° C. Above this level of magnesium substitution the product was reported to be completely amorphous. At most, 7 atom-percent (about 1.7 wt %) of magnesium ions were reported to be capable of substitution for calcium in the HAp lattice structure.
A need exists for crystalline Mg-HAp powders with a higher magnesium content, a higher degree of magnesium-substitution in the HAp lattice structure, as well as a simple and inexpensive synthesis of Mg-HAp.